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Cited by 1,365Single-cell and spatial transcriptomicsNeuroscience and Neuropharmacology ResearchCell Image Analysis Techniques

Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region

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Moffitt, Jeffrey R., Bambah-Mukku, Dhananjay, Eichhorn, Stephen W., Vaughn, Eric, Shekhar, Karthik, Perez, Julio D., Rubinstein, Nimrod D., Hao, Junjie +3 more·2018·Science
DOI 10.1126/science.aau5324PMC PMC6482113
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Abstract

The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei-including the molecular identity, spatial organization, and function of distinct cell types-is poorly understood. Here, we developed an imaging-based in situ cell-type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations, and defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for mechanistic investigation of behavior circuits. The approach described opens a new avenue for the construction of cell atlases in diverse tissues and organisms.

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  • Multiplex FISH is already used to measure the proportions of transcriptomic types in brain tissue.

    “In addition, multiplex FISH is already being used to measure the proportions of transcriptomic types within a given brain tissue (Hodge et al., 2019; Moffitt et al., 2018; Zhang et al., 2020).”

    From Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells (2020) · cites this paper as Moffitt et al., 2018

  • In mouse hypothalamus, activated neurons during a specific behavioral state are often distributed across a range of transcriptomic cell types.

    “In hypothalamus, several studies using either of the two approaches in mice demonstrate that activated neurons during a specific behavioral state are often distributed across a range of transcriptomic cell types (Kim et al., 2019; Moffitt et al., 2018; Xu et al., 2020).”

    From What is a cell type and how to define it? (2022) · cites this paper as Moffitt et al., 2018

  • Probes can be localized with diffraction-limited resolution of ~250 nm or larger, sufficient to assign transcripts within cell somata.

    “Probes can be localized with diffraction-limited resolution of ~250 nm or larger, sufficient to assign transcripts within cell somata (Moffitt et al., 2018; Zhang et al., 2020a).”

    From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Moffitt et al., 2018

  • Fine-grained cell type resolution was achieved despite probing only 155 genes, suggesting neuron types can often be defined by a modest set of judiciously chosen mRNA targets.

    “Notably, fine-grained cell type resolution was achieved despite probing only 155 genes, suggesting that neuron types can often be defined by a modest set of judiciously chosen mRNA targets.”

    From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Moffitt et al., 2018

  • Spatial maps of ~1 million cells in hypothalamic preoptic region revealed over 70 molecularly distinct cell types.

    “Spatial maps of ~1 million cells in the hypothalamic preoptic region revealed over 70 molecularly distinct cell types (Moffitt et al., 2018).”

    From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Moffitt et al., 2018

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Research works printed but not linked: 93

  1. [1]Swanson LW. Brain Res 886, 113– 164 (2000). 11119693
  2. [2]Simerly RB, in The rat nervous system, Paxinos G, Ed. (Elsevier, ed. 3rd, 2004), pp. 335– 368.
  3. [3]Sternson SM. Neuron 77, 810– 824 (2013). 23473313 PMC4306350
  4. [4]Lu J J. Neurosci 22, 4568– 76 (2002). 12040064 PMC6758802
  5. [5]Wu Z, Autry AE, Bergan JF, Watabe-Uchida M, Dulac CG. Nature 509, 325– 330 (2014). 24828191 PMC4105201
  6. [6]Scott N, Prigge M, Yizhar O, Kimchi T. Nature 525, 519– 22 (2015). 26375004
  7. [7]Sokolowski K Neuron 86, 403– 416 (2015). 25864637 PMC4484744
  8. [8]Tan CL Cell 167, 47– 59. e15 (2016). 27616062 PMC5062957
  9. [9]Leib DE Neuron 96, 1272– 1281. e4 (2017). 29268095 PMC5940335
  10. [10]Allen WE Science 357, 1149– 1155 (2017). 28912243 PMC5723384
  11. [11]Chung S Nature 545, 477– 481 (2017). 28514446 PMC5554302
  12. [12]Poulin JF, Tasic B, Hjerling-Leffler J, Trimarchi JM, Awatramani R. Nat. Neurosci 19, 1131– 1141 (2016). 27571192
  13. [13]Tanay A, Regev A. Nature 541, 331– 338 (2017). 28102262 PMC5438464
  14. [14]Zeng H, Sanes JR. Nat. Rev. Neurosci 18, 530– 546 (2017). 28775344
  15. [15]Lein E, Borm LE, Linnarsson S. Science 358, 64– 69 (2017). 28983044
  16. [16]Crosetto N, Bienko M, van Oudenaarden A. Nat. Rev. Genet 16, 57– 66 (2015). 25446315
  17. [17]Levsky JM, Shenoy SM, Pezo RC, Singer RH. Science 297, 836– 40 (2002). 12161654
  18. [18]Ke R Nat. Methods 10, 857– 860 (2013). 23852452
  19. [19]Lee JH Science 343, 1360– 1363 (2014). 24578530 PMC4140943
  20. [20]Chen KH, Boettiger AN, Moffitt JR, Wang S, Zhuang X. Science 348, aaa6090 (2015). 25858977 PMC4662681
  21. [21]Shah S, Lubeck E, Zhou W, Cai L. Neuron 92, 342– 357 (2016). 27764670 PMC5087994
  22. [23]Greenberg ME, Ziff EB, Greene LA. Science 234, 80– 83 (1986). 3749894
  23. [24]Femino AM, Fay FS, Fogarty K, Singer R. Science 280, 585– 590 (1998). 9554849
  24. [25]Raj A, van den Bogaard P, Rifkin SA, van Oudenaarden A, Tyagi S. Nat. Methods 5, 877– 879 (2008). 18806792 PMC3126653
  25. [26]Moffitt JR Proc. Natl. Acad. Sci 113, 14456– 14461 (2016). 27911841 PMC5167177
  26. [27]Klein AM Cell 161, 1187– 1201 (2015). 26000487 PMC4441768
  27. [28]Macosko EZ Cell 161, 1202– 1214 (2015). 26000488 PMC4481139
  28. [30]Levine JH Cell 162, 184– 197 (2015). 26095251 PMC4508757
  29. [31]Shekhar K Cell 166, 1308– 1323. e30 (2016). 27565351 PMC5003425
  30. [32]Wojcik SM Neuron 50, 575– 587 (2006). 16701208
  31. [33]Romanov RA Nat. Neurosci 20, 176– 188 (2017). 27991900 PMC7615022
  32. [34]Shabel SJ, Proulx CD, Piriz J, Malinow R. Science 345, 1494– 1498 (2014). 25237099 PMC4305433
  33. [35]Lein ES Nature 445, 168– 176 (2007). 17151600
  34. [36]Tasic B Nat. Neurosci 19, 335– 346 (2016). 26727548 PMC4985242
  35. [37]Shimogori T Nat Neurosci 13, 767– 775 (2010). 20436479 PMC4067769
  36. [38]Knight ZA Cell 151, 1126– 1137 (2012). 23178128 PMC3839252
  37. [39]Simerly RB. Annu. Rev. Neurosci 25, 507– 536 (2002). 12052919
  38. [40]Moffitt JR Proc. Natl. Acad. Sci 113, 11046– 11051 (2016). 27625426 PMC5047202
  39. [41]V Wu M Cell 139, 61– 72 (2009). 19804754 PMC2851224
  40. [42]Xu X Cell 148, 596– 607 (2012). 22304924 PMC3326403
  41. [43]Gregg C Science 329, 643– 648 (2010). 20616232 PMC3005244
  42. [44]Kudo T J Neurosci 32, 18035– 18046 (2012). 23238719 PMC6621739
  43. [45]Paxinos G, Franklin K, The Mouse Brain in Stereotaxic Coordinates (Academic Press Inc., San Diego, ed. 3rd, 2007).
  44. [46]Tsuneoka Y Front. Neuroanat 11, 26 (2017). 28396628 PMC5366752
  45. [47]Marlin BJ, Froemke RC. Dev. Neurobiol 77, 169– 189 (2017). 27626613
  46. [48]Zelikowsky M Cell 173, 1265– 1268. e19 (2018). 29775595 PMC5967263
  47. [49]Andero R, Dias BG, Ressler KJ. Neuron 83, 444– 454 (2014). 24976214 PMC4103970
  48. [50]Tsuneoka Y J Comp Neurol 521, 1633– 1663 (2013). 23124836
  49. [51]Gallopin T Nature 404, 992– 995 (2000). 10801127
  50. [52]Lu J, a Greco M, Shiromani P, Saper CB. J. Neurosci 20, 3830– 42 (2000). 10804223 PMC6772663
  51. [53]Zhao Z Proc. Natl. Acad. Sci 114, 2042– 2047 (2017). 28053227 PMC5338448
  52. [54]Sisk CL, Foster DL. Nat. Neurosci 7, 1040– 1047 (2004). 15452575
  53. [55]Yoon H, Enquist LW, Dulac C. Cell 123, 669– 682 (2005). 16290037
  54. [56]Boehm U, Zou Z, Buck LB. Cell 123, 683– 695 (2005). 16290036
  55. [57]George JT, Seminara SB. Endocrinology 153, 5130– 6 (2012). 23015291 PMC3473216
  56. [58]Padilla SL, Johnson CW, Barker FD, Patterson MA, Palmiter RD. Cell Rep 24, 271– 277 (2018). 29996088 PMC6094949
  57. [59]Vom Saal FS. Physiol. Behav 34, 7– 15 (1985). 4041052
  58. [60]Kohl J Nature 556, 326– 331 (2018). 29643503 PMC5908752
  59. [61]Dulac C, O’Connell LA, Wu Z. Science 345, 765– 70 (2014). 25124430 PMC4230532
  60. [62]Campbell Teskey G, Kavaliers M. Pharmacol. Biochem. Behav 31, 43– 52 (1988). 3252259
  61. [63]Fang Y-Y, Yamaguchi T, Song SC, Tritsch NX, Lin D. Neuron 98, 192– 207. e10 (2018). 29621487 PMC5890946
  62. [64]Wei Y-C Nat. Commun 9, 279 (2018). 29348568 PMC5773506
  63. [65]Arber S. Neuron 74, 975– 989 (2012). 22726829
  64. [66]Paul A Cell 171, 522– 539. e20 (2017). 28942923 PMC5772785
  65. [67]Li H Cell 171, 1206– 1220. e22 (2017). 29149607 PMC6095479
  66. [68]Chen R, Wu X, Jiang L, Zhang Y. Cell Rep 18, 3227– 3241 (2017). 28355573 PMC5782816
  67. [69]Zeisel A Cell 174, 999– 1014. e22 (2018). 30096314 PMC6086934
  68. [70]Campbell JN Nat. Neurosci 20, 484– 496 (2017). 28166221 PMC5323293
  69. [71]Blackshaw S J. Neurosci 30, 14925– 14930 (2010). 21068293 PMC6633850
  70. [72]Kimchi T, Xu J, Dulac C. Nature 448, 1009– 1014 (2007). 17676034
  71. [73]Pandey S, Shekhar K, Regev A, Schier AF. Curr. Biol 28, 1052– 1065. e7 (2018). 29576475 PMC6042852
  72. [74]Stowers L, Holy TE, Meister M, Dulac C, Koentges G. Science 295, 1493– 1500 (2002). 11823606
  73. [76]Horii-Hayashi N, Sasagawa T, Matsunaga W, Nishi M. Neural Plast 2015, 1– 12 (2015). PMC4663360 26649203
  74. [77]Ilicic T Genome Biol 17, 1– 15 (2016). 26887813 PMC4758103
  75. [78]Van Den Brink SC Nat. Methods 14, 935– 936 (2017). 28960196
  76. [79]Buettner F Nat. Biotechnol 33, 155– 160 (2015). 25599176
  77. [81]Subramanian A Proc. Natl. Acad. Sci 102, 15545– 15550 (2005). 16199517 PMC1239896
  78. [82]Perez JD Elife 4, 41 (2015).
  79. [83]Wang G, Moffitt JR, Zhuang X. Sci. Rep 8, 1– 13 (2018). 29670197 PMC5906440
  80. [84]Rasnik I, McKinney SA, Ha T. Nat. Methods 3, 891– 3 (2006). 17013382
  81. [85]Aitken CE, Marshall RA, Puglisi JD. Biophys. J 94, 1826– 35 (2008). 17921203 PMC2242739
  82. [86]Wu TJ, Gibson MJ, Rogers MC, Silverman AJ. J. Neurobiol 33, 983– 98 (1997). 9407018
  83. [87]Gottsch ML Endocrinology 145, 4073– 4077 (2004). 15217982
  84. [88]Maclusky NJ, Naftolin F. Science 211, 1294– 1303 (1981). 6163211
  85. [89]Lenz KM, Nugent BM, Haliyur R, McCarthy MM. J. Neurosci 33, 2761– 72 (2013). 23407936 PMC3727162
  86. [90]Juntti SA Neuron 66, 260– 72 (2010). 20435002 PMC2923659
  87. [91]Sherin JE, Elmquist JK, Torrealba F, Saper CB. J. Neurosci 18, 4705– 21 (1998). 9614245 PMC6792696
  88. [92]McHenry JA Nat. Neurosci 20, 449– 458 (2017). 28135243 PMC5735833
  89. [93]Hellier V Nat. Commun 9, 400 (2018). 29374161 PMC5786055
  90. [94]Park S-G Nat. Neurosci 21, 364– 372 (2018). 29379117
  91. [95]Jennings JH Nature 496, 224– 8 (2013). 23515155 PMC3778934
  92. [96]Abbott SBG, Saper CB. J. Physiol 595, 6569– 6583 (2017). 28786483 PMC5638873
  93. [97]Augustine V Nature 555, 204– 209 (2018). 29489747 PMC6086126

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Authors
Moffitt, J. R., Bambah-Mukku, D., Eichhorn, S. W., Vaughn, E., Shekhar, K., Perez, J. D., Rubinstein, N. D., Hao, J., Regev, A., Dulac, C., & Zhuang, X.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Broad Institute (US)
Corresponding author
  • Moffitt, Jeffrey R.
  • Bambah-Mukku, Dhananjay
  • Eichhorn, Stephen W.
  • Vaughn, Eric
  • Dulac, Catherine
  • Zhuang, Xiaowei
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2018-11-16
Volume
362
Issue
6416
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aau5324
PMC
PMC6482113
OpenAlex
W2899224111
Cited by
1,365
References
97
Citations by year
2026: 178 · 2025: 243 · 2024: 205 · 2023: 148 · 2022: 161 · 2021: 207 · 2020: 147 · 2019: 67 · 2018: 6
FWCI
38.14
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (R01HD082131, K99EY028625)
  • Howard Hughes Medical Institute
  • National Institute of Mental Health (R01MH113094, R01MH111502)
  • National Institute of Child Health and Human Development (1K99HD092542-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
Keywords
hypothalamus, cell atlas, single-cell RNA sequencing, spatial transcriptomics, neuronal populations, social behavior, sex differences, mice
MeSH terms
Animals, Atlases as Topic, Female, Male, Neurons, Preoptic Area, Social Behavior, In Situ Hybridization, Fluorescence, Sequence Analysis, RNA, Galanin, Gene Expression Profiling, Pituitary Adenylate Cyclase-Activating Polypeptide, Mice, Single-Cell Analysis

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